Normal structure and function of cartilage require the presence and interaction of specific gene products in the matrix. Chondrodystrophy, in its various forms, may represent specific alterations of the matrix components. Animal models of human birth defects are of value because they permit the examination of the developmental and biochemical mechanisms by which defects are produced. Chondrodysplasia (cho), by virtue of being a recessive disorder in mice that affects cartilage of the limbs, ribs, mandible and trachea (Seegmiller et al., 1971, 1972), may serve as a model for the study of human chondrodystrophy. Although the syndrome results from defective hyaline cartilage, the molecular basis of this disorder is not known. The amount of proteoglycan synthesized by cho chondrocytes appears normal, but the proteoglycan is more readily extracted by water than that of control (Stephens and Seegmiller, 1976). Collagen in the matrix appears atypical, i.e., large banded fibrils are conspicuously absent. In vitro experiments outlined in this proposal are designed to examine in further detail the capability of mutant chondrocytes to produce chondroitin-sulfate-proteoglycan. Aggregation of proteoglycan with hyaluronic acid, and the ratio of 6, 4 and 0 disaccharides produced will be examined with 35SO, and (3H)glucosamine. Biosynthetic rate, type and post-translational modification of collagen synthesized by explanted rib cartilage will be examined with (3H)proline, (3H)lysine, and (3H)glycine. The relation between any observed changes in molecular synthesis or composition and previously reported alterations of matrix structure will be explored.